UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
☒ANNUAL REPORT PURSUANT TO SECTION 13
OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2025
or
☐TRANSITION REPORT PURSUANT TO SECTION
13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from to
Commission File Number: 001-36694
Protara Therapeutics, Inc.
(Exact name of registrant as specified in its charter)
345 Park Avenue South
3rd Floor
New York, NY
(Address of Principal Executive Offices)
10010
(Zip Code)
(646)844-0337
(Registrant’s telephone number, including
area code)
Securities registered pursuant to Section 12(b)
of the Act:
Title of each class Trading Symbol(s) Name of each exchange on which registered
Common Stock, par value $0.001 per share TARA The Nasdaq Global Market
Securities registered pursuant to Section 12(g)
of the Act: None
Indicate by check mark if the registrant is a
well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒
Indicate by check mark if the registrant is not
required to file reports pursuant to Section 13 or 15(d) of the Act. Yes ☐ No ☒
Indicate by check mark whether the registrant
(1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months
(or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements
for the past 90 days. Yes ☒ No ☐
Indicate by check mark whether the registrant
has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405
of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes
☒ No ☐
Indicate by check mark whether the registrant
is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company.
See definitions of “large accelerated filer”, “accelerated filer”, “smaller reporting company” and
“emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ Smaller reporting company ☒
Emerging growth company ☐
If an emerging growth company, indicate by check
mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting
standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant
has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial
reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or
issued its audit report. ☐
If securities are registered pursuant to Section
12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction
of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error
corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s
executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by check mark whether the registrant
is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒
As of June 30, 2025, the last business day of
the registrant’s most recently completed second fiscal quarter, the aggregate market value of the registrant’s common stock
held by non-affiliates of the registrant was approximately $112.3 million, based on the closing price of the registrant’s common
stock on the Nasdaq Global Market on June 30, 2025 of $3.03 per share.
As of March 5, 2026, 54,084,378 shares of the registrant’s
common stock, $0.001 par value, were outstanding.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the registrant’s definitive
Proxy Statement to be filed with the Securities and Exchange Commission by April 30, 2026 are incorporated by reference into Part III
of this report.
PROTARA THERAPEUTICS, INC.
TABLE OF CONTENTS
FORM 10-K
For the Year Ended December 31, 2025
Page
PART I
Item 1. Business 4
Item 1A. Risk Factors 38
Item 1B. Unresolved Staff Comments 75
Item 1C. Cybersecurity 75
Item 2. Properties 77
Item 3. Legal Proceedings 77
Item 4. Mine Safety Disclosures 77
PART II
Item 6. Reserved 78
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 84
Item 8. Financial Statements and Supplementary Data 85
Item 9A. Controls and Procedures 114
Item 9B. Other Information 115
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 115
PART III
Item 10. Directors, Executive Officers and Corporate Governance 116
Item 11. Executive Compensation 116
Item 14. Principal Accountant Fees and Services 116
PART IV
Item 15. Exhibits and Financial Statement Schedules 117
i
PART I
FORWARD-LOOKING STATEMENTS
This Annual Report on Form
10-K, including the sections entitled “Business,” “Risk Factors,” and “Management’s
Discussion and Analysis of Financial Condition and Results of Operations” and our other publicly available documents contain
forward-looking statements or incorporate by reference forward-looking statements within the meaning of Section 27A of the Securities
Act of 1933, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended, or the Exchange Act, and are subject
to the safe harbor created thereby under the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all
statements other than statements of historical facts, including statements regarding our business, operations and financial performance
and conditions, as well as our plans, objectives and expectations for our business operations and financial performance and condition.
These statements relate to future events or to our future financial performance and involve known and unknown risks, uncertainties and
other factors which may cause our actual results, performance or achievements to be materially different from any future results, performance
or achievements expressed or implied by the forward-looking statements. You can generally identify these forward-looking statements by
terminology such as “believes,” “expects,” “potential,” “continues,” “may,”
“will,” “should,” “seek,” “approximately,” “predict,” “intend,”
“plans,” “estimates,” “anticipates” or the negative version of these terms or other comparable terminology.
Forward-looking statements inherently involve many risks and uncertainties that could cause actual results to differ from those expressed
in forward-looking statements. Forward-looking statements are based on management’s current plans and expectations, expressed in good
faith and believed to have a reasonable basis. However, we can give no assurance that any expectation or belief will result or will be
achieved or accomplished. Investors therefore should not place undue reliance on forward-looking statements.
These forward-looking statements include,
but are not limited to, statements about:
● expectations regarding the safety and efficacy of our product candidates;
● expectations regarding the timing, costs and outcomes of our clinical trials;
● expectations regarding potential market size;
● developments and projections relating to our competitors and industry;
1
● our ability to remain listed on the Nasdaq Global Market, or Nasdaq;
● the timing or likelihood of regulatory filings and approvals;
● our ability to protect our intellectual property position; and
Investors should also carefully
read the factors described under Item 1A. “Risk Factors” in this Annual Report on Form 10-K for a description of certain risks
that could, among other things, cause our actual results to differ from those expressed in forward-looking statements. Investors should
understand that it is not possible to predict or identify all such factors and should not consider the risks described above and under
Item 1A. “Risk Factors” to be a complete statement of all potential risks and uncertainties.
All forward-looking statements
speak only as of the date of this Annual Report and are expressly qualified in their entirety by the risk factors and cautionary statements
included in this Annual Report. Except as is required by law, we expressly disclaim any obligation to publicly release any revisions to
forward-looking statements to reflect events after the date of this Annual Report.
2
SUMMARY OF RISKS AFFECTING
OUR BUSINESS
Below is a summary of the
principal factors that make an investment in our securities speculative or risky. This summary does not address all of the risks that
we face. Additional discussion of the risks and uncertainties summarized in this risk factor summary, and other risks and uncertainties
that we face, are set forth in Part I, Item 1A. Risk Factors, and should be carefully considered, together with other information in
this Annual Report on Form 10-K and our other filings with the U.S. Securities and Exchange Commission, or SEC, before making investment
decisions regarding our securities.
● We have a limited operating history and have never generated any revenues.
3
Item 1. Business.
Overview
We are a New York City based
clinical-stage biopharmaceutical company committed to advancing transformative therapies for the treatment of cancer and rare diseases.
We were founded on the principle of applying modern scientific, regulatory or manufacturing advancements to established mechanisms in
order to create new development opportunities. We prioritize creativity, integrity and tenacity to expedite our goal of bringing life-changing
therapies to people with limited treatment options.
Our portfolio includes two
development programs utilizing TARA-002, an investigational cell therapy based on the broad immunopotentiator, OK-432, which was originally
granted marketing approval by the Japanese Ministry of Health and Welfare as an immunopotentiating cancer therapeutic agent. This cell
therapy is currently approved in Japan and Taiwan for lymphatic malformations, or LMs, and multiple oncologic indications. We have secured
worldwide rights to the asset excluding Japan and Taiwan and are exploring its use in oncology and rare disease indications. TARA-002
was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432 (marketed as Picibanil®
in Japan by Chugai Pharmaceutical Co., Ltd., or Chugai Pharmaceutical). We are currently developing TARA-002 in non-muscle invasive bladder
cancer, or NMIBC, and LMs. We are also pursuing IV Choline Chloride, an investigational phospholipid substrate replacement therapy, for
patients receiving parenteral support, or PS, which includes both nutrition and fluids.
Neither TARA-002 nor IV Choline
Chloride have been approved by the FDA or other comparable regulatory authorities for use for any indications. We have devoted substantial
efforts to the development of both TARA-002 and IV Choline Chloride and, to date, have not generated any revenues from product sales.
We do not expect to generate revenues in the near-term, and it is possible we may never generate revenues in the future. To finance our
current strategic plans, including the conduct of ongoing and future clinical trials and further research and development, we will need
to raise additional capital. See “Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations—Liquidity
and Capital Resources” for additional information about our liquidity and capital resource needs.
TARA-002 in NMIBC
Our lead oncology program is
TARA-002 in NMIBC, which is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder
muscle. Bladder cancer is the sixth most common cancer in the U.S., with NMIBC representing approximately 80% of bladder cancer diagnoses.
Approximately 65,000 patients are diagnosed with NMIBC in the U.S. each year. Very few new therapeutics have been approved for NMIBC since
the 1990s and the current standard of care for NMIBC includes intravesical Bacillus Calmette-Guérin, or BCG.
Following the completion of our ADVANCED-1 and ADVANCED-1EXP trials
in October 2024 and September 2024, respectively, to evaluate safety, preliminary efficacy and the dosing of TARA-002, at the 40KE (Klinische
Einheit, or KE, is a German term indicating a specified weight of dried cells in vial) dose level, we initiated and are currently conducting
our ADVANCED-2 clinical trial. ADVANCED-2 is a Phase 2 open-label clinical trial evaluating intravesical TARA-002 in patients with high-grade
carcinoma in situ, or CIS. Cohort A of the Phase 2 trial has completed enrollment and enrolled 31 patients with CIS (± Ta/T1, with
Ta defined as non-invasive papillary carcinoma and T1 defined as carcinoma invading the lamina propria) who are either BCG-Naïve
or BCG-Exposed and who have not received intravesical BCG for at least 24 months prior to CIS diagnosis. Cohort B of the Phase 2 trial
is expected to enroll 75 to 100 patients with BCG-Unresponsive CIS (± Ta/T1) and is designed to be registrational based on the
FDA’s August 2024 Draft Guidance for Industry on BCG-Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biological
Products for Treatment. Trial subjects in ADVANCED-2 receive an induction course, with or without a reinduction, of six weekly intravesical
instillations of TARA-002, followed by a maintenance course of three weekly instillations every three months.
4
In February 2026, we presented
updated interim data from our ongoing Phase 2 open-label ADVANCED-2 trial reporting results that continue to support TARA-002’s
potential as a mainstay in the NMIBC treatment landscape and demonstrating meaningful and durable activity in BCG-Unresponsive and BCG-Naïve
NMIBC patients.
The dataset includes 43 BCG-Unresponsive
patients and 31 BCG-Naïve patients who received at least 1 dose of TARA-002; 35 BCG-Unresponsive patients and 29 BCG-Naïve patients
completed at least one response assessment and were evaluable for efficacy as of a January 28, 2026 data cutoff. Complete response, or
CR, rates at the six months and 12 months landmark time points include all participants who were either evaluable at that time point or
had experienced disease progression or treatment failure prior to the scheduled visit.
For the BCG-Unresponsive cohort,
the CR rate at any time was 65.7% (23/35). The CR rate was 68.2% (15/22) at six months and 33.3% (5/15) at 12 months. Among responders,
the Kaplan-Meier, or KM, estimated probability of maintaining a CR for six months was 71.1% (95% confidence interval, or CI: 46.7, 95.5),
and 100% (5/5) maintained their CR from nine to 12 months. Re-induction therapy successfully converted most initial non-responders to
responders with durable responses: 61.5% (8/13) of re-induced patients converted to a CR at six months.
For the BCG-Naïve cohort,
the CR rate at any time was 72.4% (21/29). The CR rate was 66.7% (18/27) at six months and 57.9% (11/19) at 12 months. Among responders,
the KM estimated probability of maintaining a CR for six months was 73.1% (95% CI: 52.9, 93.4), and 100% (11/11) maintained their CR from
nine to 12 months. Re-induction therapy successfully converted most initial non-responders to responders with durable responses: 66.7%
(4/6) of re-induced patients converted to a CR at six months.
The majority of treatment-related
adverse events, or TRAEs, were Grade 1 and transient with no Grade 3 or greater TRAEs and no related serious adverse events, or SAEs,
as assessed by study investigators. No patients discontinued treatment due to TRAEs. The most commonly occurring TRAEs were dysuria (14%),
bladder spasm (9%), fatigue (7%) and micturition urgency (5%).
We expect to complete enrollment
of the BCG-Unresponsive registrational cohort of the ADVANCED-2 trial in the second half of 2026. Enrollment is complete in the BCG-Naïve
cohort of the ADVANCED-2 trial with 31 patients. In December 2025, we announced the FDA had provided written feedback supporting a proposed
registrational design for a controlled trial in BCG-Naïve patients (who have never been exposed and those who have not received BCG
within the last 24 months and are ineligible to receive BCG or contraindicated, cannot tolerate BCG, do not have access to
BCG, or refuse BCG). The FDA has agreed that BCG is not required as a comparator and that intravesical chemotherapy is an acceptable comparator
to TARA-002 in BCG-Naïve patients. The FDA also is aligned with the primary endpoint of the trial as the CR rate at month 6 with
duration of response as a key secondary endpoint. We intend to initiate the ADVANCED-3 trial in the second half of 2026. We have engaged
the FDA to determine how to include BCG-Exposed patients in our clinical trials of TARA-002, for whom no FDA-approved treatments are available
and who have limited options to access investigational treatment through clinical trials.
In addition to our existing clinical
trials in NMIBC, we plan to continue to explore the anti-tumor activity related to the administration of TARA-002 via systemic administration.
We continue to believe that combination therapy may play a meaningful role in the NMIBC treatment paradigm and intend to evaluate TARA-002
in combination with other therapies. Given what we have observed to date of TARA-002’s mechanism of action and safety profile, we
believe it has strong potential as a combination agent, and we continue to evaluate potential combination therapy options for our clinical
program. We also continue to conduct non-clinical studies on TARA-002 to better characterize the mechanism of action to help us understand
how TARA-002 may perform in potential combinations with other agents used to treat NMIBC, and to help us define other cancer targets for
TARA-002, both within urothelial cancer and other types of cancer affecting different parts of the body.
5
IV Choline Chloride for Patients
on PS
We are also pursuing IV Choline
Chloride, an investigational phospholipid substrate replacement therapy, for patients receiving PS which includes both nutrition and fluids.
Choline is a known important substrate for phospholipids that are critical for healthy liver function and also plays an important role
in modulating gene expression, cell membrane signaling, brain development, neurotransmission, muscle function and bone health. PS patients
are unable to synthesize choline from enteral nutrition sources, and there are currently no available PS formulations containing choline.
Every year in the U.S. there are approximately 90,000 people who require PS at home and of those approximately 30,000 are on long-term
PS. IV Choline Chloride has the potential to become the first FDA-approved IV choline formulation for PS patients.
An IV formulation of choline
is recommended for patients on parenteral nutrition, or PN, by the American Society for Parenteral and Enteral Nutrition, or ASPEN, in
their Recommendations for Changes in Commercially Available Parenteral Multivitamin and Multi–Trace Element Products, as well as
by the European Society for Clinical Nutrition and Metabolism, or ESPEN, in their Guideline on Home Parenteral Nutrition. IV Choline Chloride
has been granted Orphan Drug Designation, or ODD, by the FDA for the prevention and/or treatment of choline deficiency in patients on
long-term PN. The U.S. Patent and Trademark Office, or USPTO, has issued us a U.S. patent claiming a choline composition and a U.S. patent
claiming a method for treating choline deficiency with a choline composition, each with a term expiring in 2041.
In April 2024, we announced
alignment with the FDA on a registrational path forward for IV Choline Chloride. Previously, we had been pursuing an indication in intestinal
failure-associated liver disease, or IFALD, and following feedback from the FDA, are pursuing a broader indication as a source of choline
when oral or enteral nutrition is not possible, insufficient, or contraindicated. Feedback from the FDA on our IV Choline Chloride program
indicated that a single study with an endpoint of restoring choline levels in PS patients could serve as the basis for a regulatory submission
for IV Choline Chloride.
In September 2024, we presented
the results of THRIVE-1, a prospective, observational study evaluating the prevalence of choline deficiency and liver injury in patients
dependent on PS in the U.S., U.K. and Europe. The study found that 78% of patients who are dependent on PS were choline deficient, and
that 63% of choline deficient participants had liver dysfunction, including steatosis, cholestasis and hepatobiliary injury, underscoring
the need for IV Choline supplementation in this patient population.
In January 2026, we advanced
the development of IV Choline Chloride as a source of choline for adult and adolescent patients on long-term PS and initiated THRIVE-3,
a registrational Phase 3 clinical trial. THRIVE-3 is a seamless Phase 2b/3 trial with a dose confirmation portion (n=24) followed by a
double-blinded, randomized, placebo-controlled portion to assess the efficacy and safety of IV Choline Chloride over 24 weeks in adolescents
and adults on long-term PS when oral or enteral nutrition is not possible, insufficient, or contraindicated (n=100). The primary endpoint
of the clinical trial is a pharmacokinetic, or PK, endpoint measuring the change from baseline in plasma choline concentration. We also
plan to include a number of secondary endpoints related to liver, bone and memory. The FDA granted IV Choline Chloride Fast Track Designation,
or FTD, as a source of choline when oral or enteral nutrition is not possible, insufficient, or contraindicated.
TARA-002 in LMs
We are also pursuing
TARA-002 in macrocystic and mixed-cystic LMs, which are rare, non-malignant cysts of the lymphatic vascular system that primarily
form in the head and neck region of children before the age of two. In July 2020, the FDA granted Rare Pediatric Disease
Designation, or RPDD, for TARA-002 for the treatment of LMs and in May 2022 the European Commission granted
Orphan Medicinal Product Designation to TARA-002 for the treatment of LMs. In December 2025, the FDA granted both FDA Breakthrough
Therapy Designation, or BTD, and FTD for TARA-002 for the treatment of macrocystic and mixed cystic LMs in pediatric patients.
In addition to the clinical experience in Japan, we have secured the rights to a dataset from one of the largest ever conducted
Phase 2 trials in LMs, in which OK-432 was administered via a compassionate use program led by the University of Iowa to over 500
pediatric and adult patients. We have an open investigational new drug application, or IND, for TARA-002 in LMs with the Vaccines
and Related Products Division of the FDA, or Vaccines Division.
6
In October 2023, we initiated
STARBORN-1, which is a Phase 2 single-arm, open-label, prospective clinical trial to evaluate the safety and efficacy of intracystic injection
of TARA-002 for the treatment of macrocystic and mixed-cystic LMs (≥ 50% macrocystic disease) in participants six months to less than
18 years of age in the U.S. Including an age de-escalation safety lead-in, the clinical trial will enroll approximately 30 patients who
will receive up to four injections of TARA-002 spaced approximately six weeks apart. The primary endpoint of the clinical trial is the
proportion of participants with macrocystic LMs and mixed-cystic LMs who demonstrated clinical success, defined as having either a CR
(90% to 100% reduction from baseline in total LM volume) or substantial response (60% to less than 90% reduction in total LM volume) as
measured by axial imaging.
In November 2025, we announced
interim results from our ongoing Phase 2 STARBORN-1 trial evaluating TARA-002 in pediatric patients with macrocystic and mixed cystic
LMs. As of the data cutoff date of November 12, 2025, 12 patients had received at least one dose of TARA-002. Of the eight patients who
were evaluable at the eight-week post-treatment assessment, 100% achieved clinical success. 88% of patients achieved clinical success
with just one or two doses of TARA-002. Among macrocystic patients, 83% (5/6) achieved a CR, and the only mixed cystic patient treated
also achieved a CR. Two patients who reached the 32-week post-treatment assessment remain disease-free.
The safety profile of TARA-002
in this trial has been favorable, with the majority of adverse events, or AEs, being mild to moderate in severity. No SAEs were reported.
The most common AEs were swelling and fatigue, and only one patient discontinued treatment due to a Grade 2 AE of fatigue.
These results underscore
the potential of TARA-002 to address an unmet need for pediatric patients with LMs, for whom there are currently no approved therapies.
Many patients currently rely on invasive surgical procedures or off-label use of chemotherapies and chemicals, which can be associated
with high complication rates and challenging side effects, particularly in pediatric populations.
Other Potential Opportunities
We believe TARA-002 may also
have the potential to be used to treat other maxillofacial cysts based on the historical literature from the TARA-002 predecessor, OK-432,
as well as recent data from the STARBORN-1 trial in which the one pediatric patient with a ranula achieved a CR after a single 1KE injection
of TARA-002. While completing STARBORN-1 in LMs is our priority, we believe there may be an opportunity in the future to explore the potential
of TARA-002 to treat different types of maxillofacial cysts.
7
Our Product Candidate Pipeline
The following chart summarizes
the current status of our product candidate pipeline:
* Currently in pre-clinical studies to define dosing.
† Trial also includes BCG-Exposed patients
1 Subject to regulatory clearance
2 Potential expansion opportunity for NMIBC program
Our Corporate Strategy:
We are an oncology and rare
disease company focused on applying modern scientific advancements to established mechanisms to deliver efficient de-risked clinical programs.
Leveraging the drug development experience of our management team, our goal is to build a leading biopharmaceutical company focused on
bringing life-saving therapies to patients with significant unmet needs. Our current key initiatives are listed below:
1. Progress the registrational clinical
trial of TARA-002 for the treatment of BCG-Unresponsive NMIBC
Complete enrollment of ADVANCED-2
Cohort B in BCG-Unresponsive NMIBC patients with CIS.
8
2. Initiate ADVANCED-3 registrational clinical
trial of TARA-002 for the treatment of BCG-Naïve NMIBC
Complete the BCG-Naïve cohort of ADVANCED-2 for patients with
CIS and initiate the registrational ADVANCED-3 trial evaluating TARA-002 in patients with BCG-Naïve NMIBC.
3. Progress the registrational seamless
Phase 2b/3 trial evaluating IV Choline Chloride in patients receiving PS
Progress THRIVE-3, a seamless
Phase 2b/3 trial assessing the efficacy and safety of low and high dose IV Choline Chloride in adolescent and adult patients receiving
long-term PS when oral or enteral nutrition is not possible, insufficient, or contraindicated.
4. Progress the Phase 2 clinical trial of
TARA-002 in patients with macrocystic and mixed-cystic LMs; confirm with FDA the registrational pathway for TARA-002 in LMs
We initiated the STARBORN-1
Phase 2 trial evaluating TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs and expect to complete enrollment of the
trial in the second half of 2026. In addition, we expect to meet with the FDA to determine the registrational path forward for TARA-002
in LMs in the first half of 2026.
5. Build our operational capabilities to
successfully commercialize our oncology and rare disease programs
As we approach regulatory
filings and possible approvals of our oncology and rare disease investigational therapies, we intend to build our commercial infrastructure
to successfully launch and commercialize our products in key geographies where we can maximize value. Across the rare disease populations
(LMs and patients on PS) as well as bladder cancer, a high volume of patients are concentrated in a small number of centers of excellence.
We believe this concentration of treatment centers will potentially enable us to efficiently cover our addressable market with a relatively
small commercial footprint. Across our rare disease programs, there is significant unmet need and no available FDA-approved therapies
to meet the needs of these patients currently. In NMIBC, there is also a significant unmet need, and we believe TARA-002’s important
attributes, such as fast, simple administration by a nurse with no cumbersome additional steps or required safety protocols and a favorable
tolerability profile, will position the potential therapy favorably with patients and physicians versus other treatment options.
Our Pipeline
TARA-002
TARA-002, our lead program, is
an investigational cell therapy developed from the master cell line of the same genetically distinct Streptococcus pyogenes (group A,
type 3) Su strain as OK-432, a broad immunopotentiator marketed as Picibanil® in Japan by Chugai Pharmaceutical. We are using the
same regulatory starting materials as OK-432 and manufacture TARA-002 using an updated version of the same proprietary processes used
to manufacture OK-432. We have designated this product candidate as TARA-002 in order to differentiate the regulatory path in the U.S.
and other geographies from that of OK-432 in Japan.
We entered into an agreement
with Chugai Pharmaceutical in June 2019, as amended in July 2020, to support our development of TARA-002. The agreement provides us with
exclusive access to certain materials and documents relating to OK-432 including the master cell bank of Streptococcus pyogenes used in
the manufacturing of OK-432. Additionally, the agreement provides technical support during a certain period. We have utilized the materials,
proprietary manufacturing process and technical support provided by Chugai Pharmaceutical to support a contract development and manufacturing
organization, or CDMO, in the production of TARA-002 at a current Good Manufacturing Practices, or cGMP, compliant facility in the U.S.
Under the agreement with Chugai Pharmaceutical, we have sole responsibility for the development and commercialization of TARA-002 worldwide,
excluding Japan and Taiwan. This agreement is exclusive through June 17, 2030, or following any termination of the agreement by either
party.
In Japan, OK-432 is indicated
for: the treatment of lymphangiomas (LMs); the prolongation of survival time in patients with gastric cancer (postoperative cases) or
primary lung cancer in combination with chemotherapy; and the reduction of cancerous pleural effusion or ascites in patients with lung
cancer or gastrointestinal cancer respectively, head and neck cancer (maxillary cancer, laryngeal cancer, pharyngeal cancer, and tongue
cancer) and thyroid cancer that are resistant to other drugs.
9
We are developing TARA-002 for
the treatment of NMIBC and LMs initially in the U.S., and plan to also seek approval in other regions in the future and may also explore
additional indications where its utility as an immunopotentiator has been hypothesized to be of therapeutic benefit.
TARA-002 in NMIBC
Disease Overview
Bladder cancer is the sixth most
common cancer in the U.S., with NMIBC representing approximately 80% of bladder cancer diagnoses. NMIBC is cancer found in the tissue
that lines the inner surface of the bladder that has not spread into the bladder muscle. There are three subtypes of NMIBC: Ta, CIS, and
T1. Among the types of NMIBC, Ta accounts for most NMIBC cases (70%), whereas T1 and CIS account for 20% and 10%, respectively.
There are approximately 65,000
incidents of NMIBC in the U.S. every year, and based upon currently available data we believe that approximately 45% (approximately 30,000)
are made up of high-grade tumor types that are considered higher risk, and therefore candidates for immunotherapies, such as TARA-002.
In addition, NMIBC has one of the highest rates of recurrence with the five-year rate estimated at up to 70%.
Treatment
Treatment for NMIBC is typically
targeted to reduce unresectable persistence, recurrence after resection and to prevent disease progression to muscle-invasive bladder
cancer. The initial treatment for NMIBC includes cystoscopy and complete transurethral resection of the bladder tumor, or TURBT, for papillary
Ta or T1, or biopsy for CIS. A single postoperative instillation of intravesical chemotherapy is recommended in patients with low risk
of progression, and for patients with intermediate and high-risk disease, a longer course of intravesical therapy is administered. The
most efficacious intravesical agent to date has been BCG, a live attenuated form of Mycobacterium bovis. BCG has been the subject
of multiple supply shortages in the U.S. in the past decade due to the inability to meet demand to treat the large population of patients
with NMIBC. There has been a significant increase in bladder cancer recurrence and progression with an escalated number of patients who
require cystectomy. As such, with the current BCG shortage and limited effective alternate therapies or dosing strategies, there continues
to be a significant unmet need for treatment options for patients with NMIBC.
Clinical Development
Following the completion
of our ADVANCED-1 and ADVANCED-1EXP trials in October 2024 and September 2024, respectively, to evaluate safety, preliminary efficacy
and the dosing of TARA-002, at the 40KE dose level, we initiated and are currently conducting our ADVANCED-2 clinical trial. ADVANCED-2
is a Phase 2 open-label clinical trial evaluating intravesical TARA-002 in patients with high-grade CIS. Cohort A of the Phase 2 trial
has completed enrollment and enrolled 31 patients with CIS (± Ta/T1) who are either BCG-Naïve or BCG-Exposed and who have
not received intravesical BCG for at least 24 months prior to CIS diagnosis. Cohort B of the Phase 2 trial is expected to enroll 75 to
100 patients with BCG-Unresponsive CIS (± Ta/T1) and is designed to be registrational based on the FDA’s August 2024 Draft
Guidance for Industry on BCG-Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment. Trial
subjects in ADVANCED-2 receive an induction course, with or without a reinduction, of six weekly intravesical instillations of TARA-002,
followed by a maintenance course of three weekly instillations every three months.
In April 2025, we presented interim
data from our ADVANCED-2 trial with an April 16, 2025 data cutoff. The BCG-Unresponsive dataset included a total of five patients, all
of whom were six- and nine-month evaluable, and three of whom were evaluable at 12 months. The CR rate at any time in BCG-Unresponsive
patients was 100% (5/5). The CR rate in BCG-Unresponsive patients was 100% (5/5) at six months, 80% (4/5) at nine months, and 67% (2/3)
at 12 months.
The BCG-Naïve dataset
included a total of 21 patients, including 16 evaluable at six months, eight at nine months, and seven at 12 months. The CR rate at any
time in BCG-Naïve patients was 76% (16/21). The CR rate in BCG-Naïve patients was 63% (10/16) at six months, 63% (5/8) at nine
months, and 43% (3/7) at 12 months.
The majority of AEs were Grade
1 and transient with no Grade 3 or greater TRAEs, as assessed by study investigators. No patients discontinued treatment due to TRAEs.
The most common AEs were in line with typical responses to bacterial immunopotentiation, such as flu-like symptoms. The most common urinary
symptoms reflect urinary tract instrumentation effects, such as bladder spasm, burning sensation and urinary tract infection. Most bladder
irritations resolved shortly after administration or within a few hours to a few days.
10
In December 2025, we presented
updated interim data from our ADVANCED-2 trial of TARA-002 in BCG-Naïve patients. The dataset included 31 BCG-Naïve patients
who received at least one dose of TARA-002; 29 patients completed at least one response assessment and were evaluable for efficacy as
of a November 7, 2025 data cutoff. CR rates at the six months and 12 months landmark time points include all participants who were either
evaluable at that time point or had experienced disease progression or treatment failure prior to the scheduled visit. The CR rate at
any time was 72% (21/29). The CR rate was 69% (18/26) at six months and 50% (7/14) at 12 months. Among initial responders, 88% (14/16)
maintained their response through six months and 100% (3/3) through 12 months. Re-induction therapy successfully salvaged most initial
nonresponders, resulting in high conversion rates and durable responses: 80% (4/5) of re-induced patients converted to a CR at 6 months,
and 100% (4/4) of those responders maintained their CR at 12 months.
The majority of TRAEs were
Grade 1 and transient with no Grade 3 or greater TRAEs as assessed by study investigators. No patients discontinued treatment due to TRAEs.
The most commonly occurring TRAEs were dysuria (13%), fatigue (13%) and hematuria (6%).
In February 2026, we presented updated interim data from our ADVANCED-2
trial, reporting results that continue to support TARA-002.
The dataset includes 43 BCG-Unresponsive
patients and 31 BCG-Naïve patients who received at least one dose of TARA-002; 35 BCG-Unresponsive patients and 29 BCG-Naïve
patients completed at least one response assessment and were evaluable for efficacy as of a January 28, 2026 data cutoff. CR rates at
the six months and 12 months landmark time points include all participants who were either evaluable at that time point or had experienced
disease progression or treatment failure prior to the scheduled visit.
For the BCG-Unresponsive cohort,
the CR rate at any time was 65.7% (23/35). The CR rate was 68.2% (15/22) at six months and 33.3% (5/15) at 12 months. Among responders,
the KM estimated probability of maintaining a CR for six months was 71.1% (95% CI: 46.7, 95.5), and 100% (5/5) maintained their CR from
nine to 12 months. Re-induction therapy successfully converted most initial non-responders to responders with durable responses: 61.5%
(8/13) of re-induced patients converted to a CR at six months.
For the BCG-Naïve cohort,
the CR rate at any time was 72.4% (21/29). The CR rate was 66.7% (18/27) at six months and 57.9% (11/19) at 12 months. Among responders,
the KM estimated probability of maintaining a CR for six months was 73.1% (95% CI: 52.9, 93.4), and 100% (11/11) maintained their CR from
nine to 12 months. Re-induction therapy successfully converted most initial non-responders to responders with durable responses: 66.7%
(4/6) of re-induced patients converted to a CR at six months.
The majority of TRAEs were Grade
1 and transient with no Grade 3 or greater TRAEs and no related SAEs as assessed by study investigators. No patients discontinued treatment
due to TRAEs. The most commonly occurring TRAEs were dysuria (14%), bladder spasm (9%), fatigue (7%) and micturition urgency (5%).
In December 2025, we announced
that the FDA has provided written feedback supporting a proposed registrational design for a controlled trial in BCG-Naïve patients
(who have never been exposed and those who have not received BCG within the last 24 months and are ineligible to receive BCG or contraindicated,
cannot tolerate BCG, do not have access to BCG, or refuse BCG). The FDA has agreed that BCG is not required as a comparator and that intravesical
chemotherapy is an acceptable comparator to TARA-002 in BCG-Naïve patients. The FDA also is aligned with the primary endpoint of
the trial as the CR rate at month six with duration of response as a key secondary endpoint. We intend to initiate this registrational
clinical trial in the second half of 2026. We have engaged the FDA to determine how to include BCG-Exposed patients in our clinical trials
of TARA-002, for whom no FDA-approved treatments are available and who have limited options to access investigational treatment through
clinical trials.
11
Non-clinical Development
We continue to conduct non-clinical
studies on TARA-002 to better characterize the mechanism of action to help us understand how TARA-002 may perform in potential combinations
with other agents used to treat NMIBC. We have completed non-clinical studies comparing TARA-002 to BCG. Mechanistically, TARA-002 and
BCG are similar in that they are both intravesically administered broad-spectrum immune potentiators that drive a TH-1 pro-inflammatory
response and have a preference to M1 polarization. We found several important differences when we compared the two agents in non-clinical
studies that we believe make TARA-002 a potentially compelling new therapy. We found that TARA-002 is a NOD2/TLR 2 agonist (NOD2 is defined
as Nucleotide-binding oligomerization domain 2; TLR 2 is defined as toll-like receptor 2) and BCG is a toll-like receptor 4, or TLR4,
agonist. When we compared TARA-002 directly to BCG, in a cytotoxicity assay, we found that TARA-002 resulted in significantly stronger
tumor cell killing compared to BCG. We also found that TARA-002 resulted in significantly higher upregulation of key pro-inflammatory
cytokines and chemokines, including tumor necrosis factor alpha, or TNF-α, and interferon gamma, or interferon-γ. We also
observed that TARA-002 meaningfully down-regulated Interleukin-8, or IL-8, which at prolonged elevations is thought to increase risk for
tumor recurrence in bladder cancer after BCG therapy.
The approved indications
for OK-432 in Japan are based on systemic administration of the drug. There is a significant existing safety database with this route
of administration for OK-432 in Japan. In addition, we have completed subcutaneous systemic toxicology studies of TARA-002 and we are
considering a proof-of-concept study exploring systemic administration of TARA-002.
Regulatory Interactions
In October 2021, we announced
that the Office of Tissues and Advanced Therapies Division, now referred to as the Office of Therapeutic Products, of the FDA’s
Center for Biologics Evaluation and Research, or CBER, cleared our IND for TARA-002 in NMIBC.
Manufacturing
TARA-002 is manufactured using
an equivalent, but modernized, proprietary manufacturing process as is used to produce OK-432 by Chugai Pharmaceutical. We propagated
a master cell bank using the same master cell line of the genetically distinct strain of Streptococcus pyogenes (A group, type 3) Su strain
as OK-432. The bacteria is rendered inactive during the manufacturing process, consistent with the process used for OK-432. We have contracted
a cGMP compliant CDMO to manufacture TARA-002 in the U.S.
IV Choline Chloride for PS Patients
IV Choline Chloride is an
IV substrate therapy in development for patients receiving PS.
Choline is a known important
substrate for phospholipids, a source of methyl groups needed for many steps in metabolism and plays important roles in modulating gene
expression, cell membrane signaling, lipid transport, metabolism, liver health, brain development, neurotransmission, muscle function
and bone health. The only way to reliably replenish choline is through exogenous consumption. Patients receiving PS cannot sufficiently
absorb adequate levels of choline and available PS components do not contain sufficient amounts of choline to correct this deficit. The
use of choline for PS patients is included in key professional medical society recommendations, including ASPEN. IV Choline Chloride has
been granted ODD by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term PN. The FDA granted IV
Choline Chloride FTD as a source of choline when oral or enteral nutrition is not possible, insufficient, or contraindicated.
12
We have entered into a license
agreement with Dr. Alan Buchman for exclusive rights to the IND, ODD and other regulatory assets related to IV Choline Chloride, as well
as exclusive rights to the data from previously conducted Phase 1 and Phase 2 clinical trials led by Dr. Buchman.
The results of Dr. Buchman’s
randomized, controlled, Phase 2 clinical trial demonstrated that treatment with IV Choline Chloride resulted in normalization of plasma-free
choline concentrations, improvement of hepatic steatosis, and statistically significant improvement in cholestasis in patients dependent
on PS.
Disease Overview
PN typically consists of
carbohydrate (typically derived from dextrose), fat (lipid emulsion with essential fatty acids), protein (in the form of a balanced free
amino acid solution), electrolytes, trace elements, and most vitamins and essential nutrients known to be required by the human body,
with the notable exception of choline. PS is a medical treatment, representing PN plus fluids and is used to manage and treat malnourishment
and is indicated when there is impaired gastrointestinal function and contraindications to enteral nutrition. ASPEN and the Academy of
Nutrition and Dietetics’ Dietitians in Nutrition Support both recommend that choline be required in PN products (Vanek et al., 2012);
however, there are currently no FDA-approved intravenous choline chloride products. Humans can produce choline endogenously in the liver,
but the amount that the body naturally synthesizes is not sufficient to meet human needs, making it an essential nutrient. As a result,
humans must obtain choline from their diets. The development of IV Choline Chloride is intended to provide a source of choline when oral
or enteral nutrition is not possible, insufficient, or contraindicated.
Clinical Development
In Dr. Buchman’s Phase
2 randomized, double-blind, controlled 24-week clinical trial, patients (n=15) receiving nightly PN for > 85% of their nutritional
needs (for at least 12 weeks prior to entry) were randomized to receive via IV infusion (10-12 hours) their usual PN with placebo (n =
8), or PN to which 2g IV Choline Chloride was added (n = 7).
In the IV Choline Chloride
group, mean choline levels were within or greater than the estimated normal range (i.e., 6.7 to 26.9 nmol/mL) throughout the 24-week trial
and quickly returned to baseline levels when treatment was discontinued.
In September 2024, we presented
the results of THRIVE-1, a prospective, observational study evaluating the prevalence of choline deficiency and liver injury in patients
dependent on PS in the U.S., U.K. and Europe. The study found that 78% of patients who are dependent on PS were choline deficient, and
that 63% of choline deficient participants had liver dysfunction, including steatosis, cholestasis and hepatobiliary injury, underscoring
the need for IV Choline supplementation in this patient population.
In January 2026, we advanced
the development of IV Choline Chloride as a source of choline for adult and adolescent patients on long-term PS and initiated THRIVE-3.
THRIVE-3 is a seamless Phase 2b/3 trial with a dose confirmation portion (n=24) followed by a double-blinded, randomized, placebo-controlled
portion to assess the efficacy and safety of IV Choline Chloride over 24 weeks in adolescents and adults on long-term PS when oral or
enteral nutrition is not possible, insufficient, or contraindicated (n=100). The primary endpoint of the clinical trial is a PK endpoint
measuring the change from baseline in plasma choline concentration. We also plan to include a number of secondary endpoints related to
liver, bone and memory.
In addition to the studies performed by Dr. Buchman,
we have completed a number of preclinical in vitro and non-clinical pharmacology studies for IV Choline Chloride.
13
Regulatory Interactions
IV Choline Chloride has been
granted ODD by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term PN.
In April 2024, we announced
alignment with the FDA on a registrational path forward for IV Choline Chloride.
In October 2024, the FDA
granted FTD to IV Choline Chloride as a source of choline when oral or enteral nutrition is not possible, insufficient, or contraindicated.
Manufacturing
Our end-to-end manufacturing
of IV Choline Chloride is conducted in the U.S. by a cGMP compliant CDMO.
TARA-002 in LMs
Disease Overview
The International Society
for the Study of Vascular Anomalies classifies LMs as either macrocystic, microcystic, or mixed-cystic. Macrocystic and microcystic LMs
are differentiated by the size of the fluid-containing portion of the malformation. Macrocystic LMs are characteristically large, fluid-filled
cysts with a thin endothelial lining. Macrocystic LMs are composed of cysts greater than 2 cubic centimeters in size and present as a
soft, fluid-filled swelling beneath normal or slightly discolored skin. Macrocystic LMs are usually located in the antero-lateral cervical
region of the neck; however, it is possible for this type of LM to originate in other areas of the body. In contrast, microcystic LMs
have very limited internal space with a thick irregular endothelial lining. Microcystic LMs are comprised of cysts less than 2 cubic centimeters
in size and are often composed of micro-lymphatic channels that integrate and infiltrate normal soft tissue. Microcystic LMs can involve
both superficial and deep aspects including muscle and bone. Microcystic LMs can thicken or swell causing enlargement of surrounding soft
tissue and bones and can be found on any area of the skin or mucous membrane. Mixed-cystic LMs are comprised of varying degrees of both
macrocystic and microcystic LMs.
While the exact prevalence of
LMs is not known, in the U.S., the condition is thought to be present in approximately one in every 4,000 live births and we believe there
are approximately 1,400-1,800 LM cases per year.
Treatment
We are not aware of any approved
pharmacotherapies for LMs, except in Japan and Taiwan where OK-432 is approved. In Japan, for example, OK-432 has been the standard of
care for LMs for over 25 years.
Treatment of LMs varies depending
on the symptoms and complications that present themselves. The standard of care outside Japan for the treatment of LMs is either a partial
or complete surgical excision of the cysts. While surgery is the standard approach to the treatment of LMs in the head and neck, the region
is a difficult area to operate on because of the large number of important anatomical structures in the area. Major venous and arterial
trunks travel through the neck, as do important nerves. Surgery on such malformations frequently results in high rates of recurrence and
complications including life-long chronic conditions, such as damage to nerves and other important structures of the head and neck.
Clinical Development
Historical Data on OK-432, predecessor therapy
to TARA-002
When TARA-002 is administered,
it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a strong immune cascade. Neutrophils,
monocytes, and lymphocytes infiltrate the abnormal cells and various cytokines, including interleukins IL-2, IL-6, IL-10, IL-12, interferon-γ,
and TNF-α are secreted by immune cells to induce a strong inflammatory reaction and destroy the abnormal cells. In concert, these
immune activities induce a strong local inflammatory reaction in the cyst wall, resulting in fluid drainage, shrinkage and fibrotic adhesion
of the cyst.
14
A randomized, Phase 2 clinical
trial led by the University of Iowa studied the use of OK-432 in patients with LMs from 1998 to 2005. Most eligible subjects were between
six months and 18 years of age with macrocystic or mixed-cystic LMs (with ≥ 50% macrocystic disease) of the head and/or neck. There
were three treatment groups: immediate treatment, or ITG, delayed treatment, or DTG, and open label treatment group. The ITG received
treatment with OK-432 upon diagnosis. The DTG received OK-432 treatment following a six-month observation period; the cross-over design
was intended to investigate spontaneous resolution. The open-label treatment group included infants younger than six months of age, adults
older than 18 years of age, patients with LMs involving sites other than the head and neck (such as the axilla, thorax and extremities),